The virological factors, both biological and molecular, affecting the pathogenicity of murine C-type viruses of the ecotropic and recombinant MCF virus classes are under study. Differences in nucleotide sequences in the env and LTR regions distinguish leukemogenic AKR MCF viruses from their non-leukemogenic AKV ecotropic progenitor. In vitro recombinants have been constructed in which restriction enzyme segments of molecularly cloned AKV and MCF viruses were exchanged and rearranged. Oncogenicity testing of the resultant viruses indicates that gp70, p15E, and LTR sequences all contribute to some degree to leukemogenicity. Tests of in vitro recombinants between molecularly cloned Friend and Moloney MuLV indicate that control signals in the LTR region play a key role in determining virus-target cell specificity. During a study of the pathogenicity of viruses derived from wild mice, a new rapidly transforming defective virus has been isolated: biological and molecular studies are in progress.